Preparation for the production of 1,2,4-triazolylmethyl-oxiranes

ABSTRACT

The present invention relates to a process for the preparation of 1,2,4-triazol-1-ylmethyloxiranes of the formula I 
                         
in which A and B are identical or different and, independently of one another, are C 1 -C 4 -alkyl, phenyl-C 1 -C 2 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, tetrahydropyranyl, tetrahydrofuranyl, dioxanyl or phenyl, where the phenyl radical can carry one to three substituents chosen from the group: halogen, nitro, C 1 -C 4 -alkyl, C l -C 4 -alkyloxy, phenoxy, amino, C 1 -C 2 -haloalkyl or phenylsulfonyl, which comprises reacting
     a) an oxirane of the formula II   
     
       
         
         
             
             
         
       
         
         
           
             in which A and B have the meanings given above and L is a nucleophilically substitutable leaving group, with 4-amino-1,2,4-triazole of the formula III 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             to give 4-amino-1,2,4-triazolium salts of the formula IV and 
           
         
         b) deaminating the 4-amino-1,2,4-triazolium salts IV with alkali metal nitrites and acid or organic nitrites to give 1,2,4-triazol-1-ylmethyloxiranes of the formula I,
 
and to 4-aminotriazolium salts of the formula IV as intermediates.

The present invention relates to a process for the regiospecificpreparation of 1,2,4-triazol-1-yl-methyloxiranes of the formula I

in which A and B are identical or different and, independently of oneanother, are C₁-C₄-alkyl, phenyl-C₁-C₂-alkyl, C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, tetrahydropyranyl, tetrahydrofuranyl, dioxanyl orphenyl, where the phenyl radical can carry one to three substituentschosen from the group: halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkyloxy,phenoxy, amino, C₁-C₂-haloalkyl or phenylsulfonyl, where

-   a) an oxirane of the formula II

-   -   in which A and B have the meanings given above and L is a        nucleophilically substitutable leaving group, is reacted with        4-amino-1,2,4-triazole of the formula III

to give 4-amino-1,2,4-triazolium salts of the formula IV and

-   b) the 4-amino-1,2,4-triazolium salts IV are deaminated with alkali    metal nitrites and acid or organic nitrites to give    1,2,4-triazol-1-ylmethyloxiranes of the formula I.

4-Aminotriazolium salts IV are intermediates for the preparation ofazolylmethyloxiranes. Azolylmethyloxiranes are used for the manufactureof fungicidal compositions, in particular for combating cereal diseases.

EP-A 94 564, U.S. Pat. No. 4,906,652, EP-A 330132 and EP-A 334 035disclose processes for the preparation of triazolylmethyloxiranesstarting from an oxirane of the formula II and 1,2,4-triazoline presenceof a base. All of the processes were carried out at room temperature.The reaction time is 8-18 hours.

DE-A 39 36 823 describes the reaction of oxirane II with sodium1,2,4-triazolide in 5 h at 75° C. The solvents used aredimethylformamide and N-methylpyrrolidone.

The triazolation products present are worked up by precipitation withwater and/or extraction.

The prior art processes are burdened with a series of disadvantages.

During the triazolation of compounds of the formula II, in addition tothe desired 1-substituted triazoles, 4-substituted triazoles are alsoformed in amounts of 10-35%.

In addition, solvolysis and ring-opening reactions produce a number ofby-products which reduce the yield and considerably impair isolation andpurification of the desired triazolylmethyloxiranes.

To purify the isomer mixtures which forms, mention is made of:

extraction (e.g. DE-A 3218130, DE-A 3536529, DE-A 3805376, DE-A 3737888,EP-A 330132, U.S. Pat. No. 4,906,652), precipitation (e.g. DE-A3936823), chromatography (e.g. DE-A 3806089, recrystallization fromdiisopropyl ether (DE-A 3936823, U.S. Pat. No. 4,906,652), methyltert-butyl ether/n-hexane (DE-A 3805376, EP-A 330132), methyl tert-butylether (DE-A 3737888). In all cases various methods have to be combined.

The purity of the biologically effective isomers is predominantly lessthan 92%, only after complicated work-up as described above is itpossible to achieve acceptable contents of more than 94%.

It is also known from the literature that during the alkylation of4-aminotriazoles, quaternary triazolium salts IV are formed whoseacyclic amino group can be deaminated analogously to the chemistry ofcorrespondingly 1,1-substituted hydrazine derivatives, for example withsodium nitrite and HCl. Regioselectively substituted triazolederivatives are formed (Houben-Weyl, E 14,479ff).

This reaction can also be transferred to the alkylation with halomethylketones (Astleford et al. J. Org. Chem. 54,731 (1989) and is describedfor the preparation of antimycotic active ingredients, e.g. Can. Pat2.051.281).

According to EP 618,198, oxiranes react with opening of the oxirane ringto give 2-hydroxyalkyl-4-aminotriazolium salts which can be deaminated,but then lead to 2-hydroxyalkyltriazoles.

According to the presented prior art, it could therefore not be expectedthat compounds of the formula II can be reacted with 4-aminotriazoles togive 4-aminotriazolium salts in which the oxirane ring is retained.

Surprisingly, one such process for the preparation of 1-substitutedtriazolylmethyloxiranes was found by using sterically hindered oxiranesII and reacting them with 4-aminotriazoles without or in the presence ofcatalysts or auxiliaries to give a quaternary ammonium salt IV, and thensubjecting the nonalkylated 4-amino group to a deamination with alkalimetal nitrites and an acid or organic nitrites. In this process, thedesired 1-substituted triazolylmethyloxiranes forms without fractions ofimpurities or 4-substituted triazolylmethyloxiranes. The troublefreeformation of the products according to the invention had not beenexpected since, firstly, a reaction of the aminotriazole with theoxirane ring to give hydroxyalkyltriazoles was expected and, secondly,the opening of the oxirane ring in the presence of a strong acid wasalso feared.

The process according to the invention is explained in more detailbelow.

For the process according to the invention, azolylmethyloxiranes whichhave been prepared from the following starting materials are suitable.

-   a) Oxiranes of the formula II in which A and B are identical or    different and, independently of one another, are C₁-C₄-alkyl,    phenyl-C₁-C₂-alkyl, C₃-C₆-Cycloalkyl, C₃-C₆-Cycloalkenyl,    tetrahydropyranyl, tetrahydrofuranyl, dioxanyl or phenyl, where the    phenyl radical may carry one to three substituents chosen from the    group: halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkyloxy, phenoxy, amino,    C₁-C₂-haloalkyl or phenylsulfonyl, and L is a nucleophilically    substitutable leaving group. The oxiranes can be prepared as    described in EP-A 94564, U.S. Pat. No. 4,906,652, EP-A 330132, EP-A    334035 and DE 3936823.    -   Preferred starting materials carry the following substituents,        the preferences each applying on their own or in combination:    -   A and B are preferably a phenyl radical substituted by halogen,        C₁-C₄-alkyl or C₁-C₄-alkyloxy.    -   Particularly preferably, A is 4-fluorophenyl and B is        2-chlorophenyl.    -   L is a nucleophilically substituted leaving group, such as, for        example, halide, alkylsulfonate, arylsulfonate or alkyl sulfate.        Preferably, L is chloride, bromide, tosylate and mesylate. L is        particularly preferably mesylate.-   b) 4-Amino-1,2,4-triazoles of the formula III or analogous    derivatives.

The 4-aminotriazole used according to the invention is readilyaccessible from hydrazine and formamide (Houben-Weyl E 14,525).

The 4-aminotriazolium salts IV according to the invention are usuallyprepared in the presence of an organic solvent and optionally with theaddition of a catalyst or an auxiliary at temperatures between 0-150°C., preferably 50-150° C.

Preferred organic solvents include alcohols, such as methanol, ethanol,butanols, isopropanol, pentanols, hexanols, octanols, decanols, methylglycol, ethyl glycol, n-butyl glycol, ketones, such as acetone, methylethyl ketone or cyclohexanone, nitriles, such as acetonitrile orpropionitrile, esters, such as ethyl acetate, butyl acetate, organiccarbonates such as dimethyl carbonate or diethyl carbonate, nonaromaticand aromatic hydrocarbons such as cyclohexane, toluene, chlorobenzene or1,2-dichlorobenzene, ethers, such as tetrahydrofuran, dimethoxyethane,dioxane, amides, such as dimethylformamide, dimethylacetamide,N-methylpyrrolidone, tetramethylurea, and also dimethyl sulfoxide,sulfolane and corresponding mixtures.

Suitable preferred organic solvents are alcohols, such as methanol,ethanol, isomeric butanols and pentanols, isopropanol, 2-ethylhexanol,methyl glycol, ethyl glycol, n-butyl glycol and mixtures thereof withtoluene.

n-Butyl glycol, 2-ethylhexanol and mixtures thereof with toluene areparticularly preferred.

Suitable catalysts are quaternary ammonium and phosphonium salts, suchas tetrabutylammonium chloride, betaines, such as 4-dimethylsulfoniumphenoxide. Suitable auxiliaries are specific nucleophilic anions, e.g.cyanide, iodide, fluoride, amines, such as DABCO, dimethylaminopyridine,dimethylcyclohexylamine, tributylamine, triethylamine or DBU.

The catalysts are used in amounts of 0.01-5 mol % based on the oxiraneII, the auxiliaries in amounts of 5-300 mol %.

The 4-aminotriazolium salts of the formula IV can be obtained in pureform from the reaction mixtures by crystallization and/or precipitation,optionally at low temperatures below 10° C.

The 4-aminotriazolium salts of the formula IV are dissolved in water andtreated with alkali metal nitrites, such as potassium nitrite or sodiumnitrite and strong acids, such as hydrochloric acid or sulfuric acid, at−10-60° C. It is also possible to use organic nitrites, such as, forexample, n-butyl nitrite or t-butyl nitrite.

Besides the aqueous solution, the deamination can also be carried out inaqueous/organic solvent mixtures, such as water/THF, water/alcohols orwater/NMP.

In addition, it is possible to remove the solvents used by evaporationand to subject the residue to a deamination, where necessary followingremoval of the non-water-soluble components

A particular-variant involves carrying out the aminotriazolation in asolvent which has low miscibility with water, such as n-butanol,isopentanol, 2-ethylhexanol or tetrabutylurea, with simultaneous orsubsequent extraction of the quaternary salt with water.

The triazolylmethyloxiranes formed usually precipitate out of theaqueous solution during the deamination. The precipitation can becompleted by neutralization.

As a result of the process according to the invention, the ratio of1-substituted triazoles to 4-substituted triazoles (regioselectivity) isincreased to a value of more than 50. 4-Substituted triazole derivativescan often no longer be detected.

The resulting product no longer needs to be purified in a complexmanner. The content of 1-substituted triazole is usually greater than98%.

The fraction of inactive isomers and by-products has been considerablyreduced and thus the ecological efficiency of the agrochemical activeingredient is considerably increased.

The present invention further provides 4-amino-1,2,4-triazolium salts ofthe formula IV,

in which A and B are identical or different and, independently of oneanother, are C₁-C₄-alkyl, phenyl-C₁-C₂-alkyl, C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, tetrahydropyranyl, tetrahydrofuranyl, dioxanyl orphenyl, where the phenyl radical can carry one to three substituentschosen from the group: halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkyloxy,phenoxy, amino, C₁-C₂-haloalkyl or phenylsulfonyl, and in which L⁻ isthe anion of a nucleophilically substitutable leaving group, such as,for example, halide, alkylsulfonate, arylsulfonate or alkyl sulfate.

A and B are preferably a phenyl radical substituted by halogen,C₁-C₄-alkyl or C₁-C₄-alkyloxy.

Particularly preferably, A is 4-fluorophenyl and B is 2-chlorophenyl.

Preferably, L⁻ is chloride, bromide tosylate and mesylate.

L⁻ is particularly preferably mesylate.

The organic molecular moieties given for the substituents A, B and Lrepresent collective terms for individual listings of the individualgroup members. All of the hydrocarbon chains, i.e. all alkyl, alkoxy,haloalkyl, phenylalkyl, cycloalkyl, cycloalkenyl chains, may bestraight-chain or branched.

Unless stated otherwise, halogenated substituents preferably carry oneto five identical or different halogen atoms. The meaning halogen is ineach case fluorine, chlorine, bromine or iodine.

In addition, the following meanings, for example, apply:

-   -   C₁-C₄-alkyl: e.g. methyl, ethyl, propyl, 1-methylethyl, butyl,        1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl;    -   C₁-C₂-haloalkyl: a C₁-C₂-alkyl radical, as mentioned above,        which is substituted partially or completely by fluorine,        chlorine, bromine and/or iodine, thus e.g. chloromethyl,        dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl,        trifluoromethyl, chloromethyl, dichlorofluoromethyl,        chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl,        2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,        2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,        2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,        2,2,2-trichloroethyl, pentafluoroethyl.    -   C₁-C₄-alkoxy: e.g. methoxy, ethoxy, propoxy, 1-methylethoxy,        butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy;    -   phenyl-C₁-C₂-alkyl: C₁-C₂-alkyl substituted by a phenyl radical,        such as benzyl, 1-phenylethyl and 2-phenylethyl;    -   C₃-C₆-cycloalkyl: e.g. cyclopropyl, cyclobutyl, cyclopentyl or        cyclohexyl;    -   C₃-C₆-cycloalkenyl: such as C₃-C₆-cycloalkyl with a double bond,        such as cyclopropenyl, cyclobutenyl, cyclopentenyl or        cyclohexenyl.

The process according to the invention is described by the examplesbelow.

As oxirane II, in all cases a compound of the formula II with thefollowing substituents is used: L=CH₃SO₂O—, B=4-fluorophenyl andA=2-chlorophenyl.

EXAMPLE 1

142.8 g of compound II (L=MeSO₂O—, cis/trans 5:95) are heated to 100° C.with 33.6 g of 4-amino-1,2,4-triazole and 400 ml of n-butanol for 8 h.The aminotriazolium salt formed precipitates out of the reaction mixturein solid form. The conversion with regard to mesylate is more than 90%(HPLC method). After the mixture has been cooled, 110 g of4-aminotriazolium salt IV can be separated off (62% yield). The motherliquor can be used with the aminotriazolium salt which remains insolution (ca. 45 g) for a further batch.

The 4-aminotriazolium salt has an m.p.=192° C.

EXAMPLE 2

142.8 g of compound II (L=MeSO₂O—, cis/trans 5:95) are dissolved in 500ml of isopropanol and then heated for 8 h at 80° C. with 33.6 g of4-aminotriazole. A conversion of compound II of 51% is achieved, andabout 72 g of 4-aminotriazolium salt IV (80% of the reacted compound II)can be separated off from the cooled solution. The m.p. is 193° C.

An analogous experiment in the presence of 0.2 g of potassium iodidereaches a conversion of 67% after 8 h.

EXAMPLE 3

454 ml of mesylate-DMF solution, comprising 143 g of mesylate II(cis/trans 5:95) are heated at 130° C. with 33.6 g of4-amino-1,2,4-triazole and 400 ml of N-methylpyrrolidone for 2 h. Theaminotriazolium salt IV formed can, after the solvent has been removedwith reduced pressure, be purified by careful washing of the residuewith acetone/MeOH. The conversion with regard to mesylate is greaterthan 97% (HPLC method). 140 g of 4-aminotriazolium salt IV can beisolated (81% yield). The 4-aminotriazolium salt IV has an m.p.=190° C.

EXAMPLE 4

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (153 mmol) of 2-ethylhexanol is stirredfor 16 h at 80° C. 50 g of the mineralized water are then added and,after 5 min at 65° C., the phases are separated. Yield (quant. HPLC):85%.

EXAMPLE 5

A mixture of 5 g (14 mmol) of mesylate and 1.1 g (13 mmol) of4-amino-1,2,4-triazole in 20 g (148 mmol) of diglyme is stirred for 7 hat 80° C. 50 g of demineralized water are then added and, after 5 min at65° C., the phases are separated. Yield (quant. HPLC): 25%.

EXAMPLE 6

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (202 mmol) of N-methylpyrrolidone isstirred for 7 h at 100° C. 50 g of demineralized water are then addedand, after 5 min at 65° C., the phases are separated. Yield (quant.HPLC): 72%.

EXAMPLE 7

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (149 mmol) of diethylene glycol dimethylether is stirred for 7 h at 100° C. 50 g of demineralized water are thenadded and, after 5 min at 65° C., the phases are separated. Yield(quant. HPLC): 51%.

EXAMPLE 8

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (203 mmol) of cyclohexanone is stirredfor 6 h at 90° C. 50 g of demineralized water are then added and, after5 min at 65° C., the phases are separated. Yield (quant. HPLC): 2%.

EXAMPLE 9

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (153 mmol) of 1-octnol is stirred for 6 hat 80° C. 50 g of demineralized water are then added and, after 5 min at65° C., the phases are separated. Yield (quant. HPLC): 65%.

EXAMPLE 10

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (227 mmol) of ethylene carbonate isstirred for 6 h at 80° C. 50 g of demineralized water are then addedand, after 5 min at 65° C., the phases are separated. Yield (quant.HPLC): 27%

EXAMPLE 11

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of 4amino-1,2,4-triazole in 20 g (194 mmol) of benzonitrile is stirred for 6h at 80° C. 50 g of demineralized water are then added and, after 5 minat 65° C., the phases are separated. Yield (quant. HPLC): 49%

EXAMPLE 12

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (200 mmol) of cyclohexanol is stirred for17 h at 80° C. 50 g of demineralized water are then added and, after 5min at 65° C., the phases are separated. Yield (quant. HPLC): 29%

EXAMPLE 13

A mixture of 5 g (14 mmol) of mesylate and 1.4 g (17 mmol) of4-amino-1,2,4-triazole in 20 g (136 mmol) of 1,2-dichlorobenzene isstirred for 16 h at 80° C. 50 g of demineralized water are then addedand, after 5 min at 65° C., the phases are separated. Yield (quant.HPLC): 21%

EXAMPLE 14

At 90° C. and 130 mbar, 356.8 g (1.0 mol) of mesylate in 2020 g oftoluene are metered into a solution of 252.2 g (3.0 mol) of 4amino-1,2,4-triazole in 1070.4 g (8.4 mol) of n-butyl glycol. Meteringand distillation are complete after a minimum of 6 h and then left tocool to 85° C. The temperature is then decreased to 65° C. with a rampof 3 K/h. After cooling the resulting mash to 25° C., the suspension isthen filtered through a suction filter Yield (quant. HPLC): 98%

EXAMPLE 15

At 90° C. and 130 mbar, 121 g (0.34 mol) of mesylate in 679 g of tolueneare metered into a solution of 86.4 g (1.03 mol) of4-amino-1,2,4-triazole and 128.3 g of tri-n-butylamine (0.69 mol) in 600g g (4.7 mol) of n-butyl glycol. Metering and distillation of 556 g arecomplete after a minimum of 6 h and then left to cool to 85° C. Thetemperature is then decreased to 65° C. with a ramp of 3 K/h. Aftercooling the resulting mash to 25° C., the suspension is then filteredthrough a suction filter. Yield (quant. HPLC): 77%

EXAMPLE 16

At 90° C. and 130 mbar, 121 g (0.34 mol) of mesylate in 679 g of tolueneare metered into a solution of 86.4 g (1.03 mol) of4-amino-1,2,4-triazole and 43.2 g of tri-n-butylamine (0.34 mol) in 600g g (4.7 mol) of n-butyl glycol. Metering and distillation of 556 g arecomplete after a minimum of 6 h and then left to cool to 85° C. Thetemperature is then decreased to 65° C. with a ramp of 3 K/h. Aftercooling the resulting mash to 25° C., the suspension is then filteredthrough a suction filter. Yield (quant. HPLC): 52%

EXAMPLE 17

At 90° C. and 130 mbar, 128.2 g (0.36 mol) of mesylate in 725 g oftoluene are metered into a solution of 84.8 g (1.01 mol) of4-amino-1,2,4-triazole in 600 g (4.7 mol) of n-butyl glycol. Meteringand distillation of 631 g of toluene are complete after a minimum of 6 hand then left to cool to 85° C. The temperature is then decreased to 65°C. with a ramp of 3 K/h. After cooling the resulting mash to 25° C., thesuspension is then filtered through a suction filter. Yield (quant.HPLC): 99%

Deamination:

EXAMPLE 18

Procedure

50 mmol of solid 4-aminotriazolium salt IV (22 g,. A=4-fluorophenyl andB=2-chlorophenyl) are taken up in 150 ml of water and admixed with 110mmol of conc. hydrochloric acid (11 ml). The mixture is then cooled to0° C. A solution of 3.6 g (52 mmol) of sodium-nitrite in 50 ml of wateris slowly added dropwise at this temperature during which a gentleevolution of gas starts. When the addition is complete, the mixture isleft to warm to room temperature and then neutralized with dilutepotassium carbonate solution (−50 ml of a 15% strength aqueoussolution). The product which precipitates out is filtered off withsuction, washed with water and dried.

Yield: 95%, m.p. 136° C., content: 98.5% trans-epoxyconazole (transbased on A and B).

EXAMPLE 19

Under nitrogen, 1162.5 g (0.5 mol) of 18.9% strength aqueous triazoliumsalt solution are initially introduced and the pH is adjusted to <1.0using 18% strength hydrochloric acid. The reaction mixture is heated to60° C. Then, in parallel, 250 ml (0.8 mol) of 20% strength sodiumnitrite solution (1.6 eq) and 80 g (0.39 mol) of 18% strengthhydrochloric acid (0.8 eq) are metered in at pH 1 over a period of 1 h.The suspension is then stirred for 1.5 h at 60° C., cooled to 20° C. andneutralized with 15% strength NaOH. The suspension is then separated offvia a suction filter and the solid is dried in the vacuum drying cabinetat 20 mbar and an internal temperature of 50° C. Yield (quant. HPLC):87.8%

EXAMPLE 20

Under nitrogen, 214 g (0.05 mol) of 10.8% strength aqueous triazoliumsalt solution are initially introduced. The reaction mixture is heatedto 50° C. 7.0 g (0.065 mol) of n-butyl nitrite are then metered in overa period of 1 h. The suspension is then stirred for 1 h at 50° C.,cooled to 20° C. and separated off via a suction filter and the solid isdried in the vacuum drying cabinet at 20 mbar and an internaltemperature of 50° C. Yield (quant. HPLC): 49.0%

EXAMPLE 21

Under nitrogen, 940 g (0.13 mol) of 6.1% strength aqueous triazoliumsalt solution are initially introduced and the pH is adjusted to <1.0using 18% strength hydrochloric acid. The reaction mixture is heated to60° C. Then, in parallel, 61.3 ml (0.2 mol) of 20% strength sodiumnitrite solution (1.5 eq) and 29 g (0.39 mol) of 18% strengthhydrochloric acid (1.1 eq) are then metered in at pH 1 over a period of1 h. The suspension is then stirred for 1.5 h at 60° C., cooled to 20°C. and separated off via a suction filter and the solid is dried in thevacuum drying cabinet at 20 bar and an internal temperature of 50° C.Yield (quant. HPLC): 92.7%

EXAMPLE 22

Extraction

142.8 g of compound II are dissolved in 500 ml of n-butanol and thenheated for 7 h with 33.6 g of 4-aminotriazole. A conversion of compoundII of 83% is achieved. Following the addition of 100 ml of toluene, theorganic phase is extracted with 3×500 ml of water. The aqueous solutionis cooled to 0-5° C., acidified with 160 ml of 18% HCl and then admixedin portions with a solution of 27.6 g of sodium nitrite in 100 ml ofwater (N₂O evolution). During this admixing, a white precipitate formswhich, after washing with MeOH/water and drying at 80° C., gives 65 g ofisomer-free trans-poxyconazole. From the mother liquor it is possible,following neutralization with 2N NaOH, to obtain about a further 18 g ofimpure epoxyconazole.

Yield of pure product based on compound II: 59.3%, content: 97.9%trans-epoxyconazole, m.p. of 136° C.

The organic phase can be used for a further batch, the toluene addedbeing recovered by distillation and only added again during theextraction.

EXAMPLE 23

142.8 g of compound II are dissolved in 500 ml of n-butanol and thenheated for 12 h with 33.6 g of 4-aminotriazole. A conversion of compoundII of 97% is reached. Following the careful removal of the solvent at 8mbar and 60° C., the residue is dissolved in 1000 of water and unreactedcompound II is extracted twice with 100 ml of toluene.

The aqueous solution is cooled to 0-5° C., acidified with 160 ml of 18%HCl and then admixed in portions with a solution of 27.6 g of sodiumnitrite in 100 ml of water (N₂O evolution). During the admixing, a whiteprecipitate forms. After 4 h, the mixture is neutralized with potassiumcarbonate solution and filtered with suction. After washing withMeOH/water and drying at 80° C., 143 g of isomer-freetrans-epoxyconazole are obtained.

Yield: 83% m.p. 136° C. Content: 98.7%

EXAMPLE 24

Extractive One-pot Reaction

Procedure:

35.6 g of compound II (L=MeSO₂O—, cis/trans 5:95, 100 mmol) are taken upin 200 ml of tetrabutylurea and admixed with 8.8 g (105 mmol) of4-amino-1,2,4-triazole and 200 ml of water with the addition oftetrabutylammonium chloride. The mixture is then refluxed for 4 hours(conversion based on compound II about 30%). During this time, thereaction product dissolves in the aqueous phase, while unreacted alkylcompound and excess aminotriazole remains in the immiscible organicphase. The mixture is cooled and the aqueous phase is separated off. Theorganic phase can be returned.

The aqueous phase is admixed with 2.2 times the molar amount of conc.hydrochloric acid and cooled to 0° C. The corresponding molar amount ofsodium nitrite, dissolved in 50 ml of water, is slowly added dropwise atthis temperature, during which gentle gas evolution starts. When theaddition is complete, the mixture is warmed to room temperature and thenneutralized with dilute potassium carbonate solution. The product whichprecipitates out is filtered off with suction, washed with water anddried.

Yield (based on alkyl compound used): 8.2 g of trans-epoxyconazole (80%based on reacted compound II).

1. A process for the preparation of 1,2,4-triazol-1-yl methyloxiranes ofthe formula I

in which A and B are identical or different and, independently of oneanother, are C₁-C₄-alkyl, phenyl-C₁-C₂-alkyl, C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, tetrahydropyranyl, tetrahydrofliranyl, dioxanyl orphenyl, where the phenyl radical can carry one to three substituentschosen from the group: halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkyloxy,phenoxy, amino, C₁-C₂-haloalkyl or phenylsulfonyl, which comprisesreacting a) an oxirane of the formula II

in which A and B have the meanings given above and L is anucleophilically substitutable leaving group, with4-amino-1,2,4-triazote of the formula III

to give 4-amino-1,2,4-triazolium salts of the formula IV and b)deaminating the 4-amino-1,2,4-triazolium salts IV with alkali metalnitrites and acid or organic nitrites to give 1,2,4-triazol-1-ylmethytoxiranes of the formula I.
 2. A process as claimed in claim 1,wherein the reaction in stage a) is carried out in the presence of anorganic solvent.
 3. A process as claimed in claim 2, wherein alcohols,ketones, nitriles, esters, organic carbonates, nonaromatic and aromatichydrocarbons, ethers, amides, dimethyl sulfoxide, sulfolane or mixturesthereof are used as organic solvent.
 4. A process as claimed in eitherclaim 1 or 2, wherein the organic solvent used is methanol, ethanol,butanols, isopropanol, pentanols, hexanols, octanols, decanols, methylglycol, ethyl glycol, n-butyl glycol, acetone, methyl ethyl ketone,cyclohexanone, acetonitrile, propionitrile, ethyl acetate, butylacetate, tetrahydrofuran, dimethoxyethane, dioxane, dimethylformamide,dimethylacetamide, N-methylpyrrolidone, tetramethylurea, dimethylsulfoxide, sulfolane or mixtures thereof.
 5. A process as claimed inclaim 4, wherein the organic solvent used is n-butyl glycol,2ethylhexanol or mixtures thereof with toluene.
 6. A process as claimedin claim 1, wherein the reaction in stage a) is carried out attemperatures of from 50 to 150° C.
 7. A process as claimed in claim 1,wherein the reaction in stage a) is carried out in the presence of0.01-5 mol % of a catalyst or 5-300 mol % of an auxiliary.
 8. A processas claimed in claim 7, wherein quaternary ammonium salts, quaternaryphosphonium salts and betaines are used as catalyst and/or nucleophilicanions and amines are used as auxiliaries.
 9. A process as claimed inany of claims 7 to 8, wherein tetrabutylammonium chloride and4-dimethylsulfonium phenoxide are used as catalyst and/or cyanides,iodides, fluorides, 1,4-diaza-bicyclo[2.2.2]octan (DABCO),dimethylaminopyridine, dimethylcyclohexylamine, tributylarnine,triethylamine or 1,8-diaza-bicyclo[5.4.0]-7-undecen (DBU) are used asauxiliaries.
 10. A process as claimed in claim 1, wherein the4-aminotriazolium salts of the formula IV formed in stage a) areseparated off from the reaction mixture by precipitation and/orcrystallization.
 11. A process as claimed in claim 10, wherein theprecipitation and/or crystallization of the 4-aminotriazolium salts ofthe formula IV is carried out at temperatures below 10° C.
 12. A processas claimed in claim 1, wherein the 4-aminotriazolium salts of theformula IV formed in stage a) are extracted from the reaction mixture bycontinuous and/or discontinuous extraction.
 13. A process as claimed inclaim 12, wherein the continuous and/or discontinuous extraction iscarried out with water, optionally in the presence of a water-immiscibleorganic solvent.
 14. A process as claimed in claim 1, wherein thedeamination in stage b) is carried out in aqueous solution,water/tetrahydrofuran, water/alcohols or water/N-methyl-2-pyrrolidone.15. A process as claimed in claim 1, wherein the deamination in stage b)is carried out with organic nitrites in aqueous or organic solution orin aqueous/organic solvent mixtures such as water/tetrahydrofuran,water/alcohols, water/N-methyl-2-pyrrolidone.
 16. A process as claimedin either claim 14 or 15, wherein the deamination in stage b) is carriedout at a temperature of from −10 to 60° C.
 17. A4-amino-1,2,4-triazolium salt of the formula IV

wherein A and B are identical or different and, independently of oneanother, are C₁-C₄-alkyl, phenyl-C₁-C₂-alkyl, C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, tetrahydropyranyl, tetrahydrofuranyl, dioxanyl orphenyl, where the phenyl radical can carry one to three substituentschosen from the group: halogen, nitro, C₁-C₄-alkyl, C₁-C₄-alkyloxy,phenoxy, amino, C₁-C₂-haloalkyl or phenylsulfonyl, and wherein L is anucleophilically substitutable leaving group.
 18. The4-amino-1,2,4-triazolium salt of the formula IV as claimed in claim 17,in which A and B are identical or different and are a phenyl radicalsubstituted by halogen, C₁-C₄-alkyl or C₁-C₄-alkoxy.
 19. The4-amino-1,2,4-triazolium salt of the formula IV as claimed in claim 17,in which A is 4-fluorophenyl and B is 2-chlorophenyl.